Dominance in the Antiarsonate Response

Although idiotypic dominance was first observed over a decade ago in the antiarsonate (ABA) 1 system (1), its mechanism remains enigmatic. It was initially postulated that B cell clones expressing a dominant idiotype were preferentially expanded because they had higher affinities for antigen than their less successful competitors (2). Subsequent studies (2) showed, however, that anti-ABA antibodies expressing a dominant idiotype had median affinities for ABA, arguing persuasively against this explanation. Recent work suggests that multiple mechanisms may be responsible for idiotypic dominance. Idiotypic dominance may be established at different levels in B cell ontogeny. In the T15 system, dominance has been demonstrated as early as the pre-B cell stage (3). In other responses, including that of A strain mice to ABA, dominance is established only after the expression of surface immunoglobulin (4). In this system, CRI "+ (cross-reactive idiotope) B cells accounted for ~3% of the total number of B cells responding to ABA in nonimmune mice. Upon immunization, this frequency increased to 20-80% (4), suggesting that the CRI a+ B cells were preferentially expanded. Since this observation cannot be directly accounted for by differences in affinity (2), idiotype-specific selection is implicated. Idiotype-specific regulation could establish idiotypic dominance by either positive or negative selection of particular B cell clones. Dominance by positive selection could result from idiotype-specific helper T cells preferentially expanding clones that express a particular idiotype. Such helper cells have been reported in the CRI" (5) and other systems (6, 7). Alternatively, dominance could result